Project II Stress has been shown to alter the development of neural systems involved in learning (contextual, cued, and extinction). Moreover, emerging evidence in the human and mouse suggests that stressful experiences result in region-specific alterations in BDNF levels. The overarching goal of this project is to test the hypothesis that the Val66Met polymorphism in the BDNF gene will moderate the effects of early life stress, in the form of institutional/orphanage rearing, on the structure and function of the hippocampus, amygdala, and ventromedial prefrontal cortex (including orbital prefrontal cortex). Participants will be 12-14 year old children adopted internationally between the ages of 1 month and 5 years after having lived for 75% or more of their pre-adoption lives in institutions (hospitals, orphanage). We will test the hypothesis that BDNF Val66Met polymorphism will moderate the impact of early life stress (dose/duration of institutional care) on structure and function of these regions (Center Aim 2). We will also examine whether these effects will be diminished with time in the adoptive home (Center Aim 3). This component of Project II will parallel manipulations of environmental gain of function in the mouse model in Project III (Center Aim 3), while the environmental stressor of early institutionalization will parallel early postnatal stress in the mouse (Center Aim 2). Project II will draw on the Administrative and Data Management Core as well as the Statistical Genetics Core of the Center for support in processing and analysis of behavioral, imaging, and genetics data.